The NHGRI Bioinformatics and Scientific Programming Core actively supports the research being performed by NHGRI/DIR investigators by providing expertise and assistance in bioinformatics and computational analysis. The Core facilitates access to specialized software and hardware, develops generalized software solutions that can address a variety of questions in genomic research, develops database solutions for the efficient archiving and retrieval of experimental and clinical data, disseminates new software and database solutions to the genome community at-large, collaborates with NHGRI researchers on computationally-intensive projects, and provides educational opportunities in bioinformatics to NHGRI Investigators and trainees. Scientific projects completed in 2013-2014 include the annotation of the Mnemiopsis genome using next-generation sequencing data, the development of a human malformation terminology tool to allow clinicians to build and maintain downloadable spreadsheets of patient conditions, the development of a bioinformatic pipeline to map zebrafish retroviral integration sites using Illumina sequence tags and to identify integrations occurring within Ensembl-annotated genes; the development of a Web site and database to search for retroviral integration sites, an analysis of the effects of RRP1B knockdown on gene expression, an analysis of ChIP-seq data to identify the genomic locations of specific histone modifications in dog bladder tumor cell lines, an analysis of ChIP-seq data to investigate Sox10 transcription factor binding at enhancer sites in mouse, correlating Sox10 binding with EP300 and H3K4Me1 binding; the identification of co-varying mutations and pathways to classify tumor subtypes, a multi-species BLAST analysis to estimate cross-species sequence similarity of protein-coding genes, the development of a software pipeline to create word clouds based on SMS text responses from visitors to the Genome: Unlocking Life's Code exhibition at the Smithsonian Institution as they interact with the exhibit, and the investigation of the effect of silent mutations in splicing from the Cancer Genome Atlas RNA-seq data. Ongoing scientific projects include the detection of gene and isoform expression changes during early development in Mnemiopsis using RNA-seq data, analyses of human disease gene orthologs in Mnemiopsis, annotation of two Hydractinia genomes using next-generation sequence data, analyses of sequence traces to detect mutations in putative oncogenes in tumor samples, the development of a Web interface to return ClinSeq results to patients, a characterization of large exons in vertebrate, invertebrate, and plant genomes; ongoing updates and improvements to the Breast Cancer Information Core (BIC), identification of differentially expressed genes in samples from patients with different folate levels, analyses of RNA-seq data to investigate alternative splicing in Fanconi anemia patients, analyses of alternatively spliced genes in select tissue types over time, the identification of DNA binding sites of RRP1B by ChIP-seq, RIP-seq analysis for RRP1B immunoprecipitation, identification of a set of 500 methylation markers that classifies different types of tumors, enrichment and pathway analysis of genes identified as being differentially expressed by RNA-seq analysis, finding differentially expressed proteins from mass spectometry data, an RNA-seq analysis of 180 samples, cases and controls from the MH-GRID study; identification of changes in gene expression that occur in patients with hereditary inclusion body myopathies after treatment with neuraminidase, identification of a set of biomarkers that correlates with degree of inflammation during sepsis, determination of changes in gene expression that result from different methods of plating cells, comparisons of gene expression profiles among cohorts to assess response to gene therapy in patients with familial platelet disorder, a comparison of gene expression profiles in cells with and without MSH2 mutation after treatment with baicalein, the development and maintenance of a customized SQL database for storing and computing on large numbers of records for canine genotypes, phenotypes, sequences, variations, sample data, and pedigree data; an RNA-seq analysis in melanA and CoCl2-treated mouse cells, performing ChIP-seq analyses using the MACS pipeline, performing comparisons of gene expression profiles of induced stem cells to melanocytes, identification of gene expression changes in cells from NPC patients treated with different drug regimens, the development of a Web-based survey studying how women feel about the techniques doctors use to talk with patients about their weight (part of the Weight Management Interaction Study), measurement of gene expression changes in thymocytes over four different stimulations and four different mutations, biomarker selection of targets from RNAi screens, the identification of differentially expressed genes after GBA knockdown in Gaucher disease, the discovery of differentially expressed genes in patients with methylmalonic acidemia, and the identification of changes in gene expression in male and female patients with methylmalonic acidemia and homocysteinemia (cblX type). On the educational front, Drs. Baxevanis and Wolfsberg continue to serve as co-directors of the Current Topics in Genome Analysis lecture series. The 11th offering of this course in 2014 consisted of 14 1.5-hour sessions on successive Wednesdays, with a mixture of local and outside speakers covering the major areas of genomics. (Besides serving as the Course Directors, Drs. Baxevanis and Wolfsberg also give three of the lectures in the series themselves.) Given the diverse audience attending these lectures, the lectures have been geared towards first-year graduate students, with an emphasis on practical rather than theoretical approaches. Handouts and reference lists are provided for each lecture, and ample time is allotted at the end of each lecture for questions and discussion. Over the years, Drs. Baxevanis and Wolfsberg have made sure that the lecture series keeps pace with changes in genomic technologies and approaches, as evidenced by how the syllabus for the course has evolved with each offering, incorporating new aspects of genomics and bioinformatics that have emerged as important over time. The best measure of the popularity of this course is in the numbers. Through the use of social media technologies such as YouTube and coverage through various Facebook and Twitter feeds, the reach of the course has gone well-beyond the Bethesda campus, with over 525,000 YouTube views of the lectures from the 2010-2014 series to date.